Phase II trial of alemtuzumab, dexamethasone and lenalidomide followed by randomisation to lenalidomide maintenance versus no further treatment for high-risk CLL NCRI CLL210)
| ISRCTN | ISRCTN40303610 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN40303610 |
| EudraCT/CTIS number | 2010-019575-29 |
| Secondary identifying numbers | 9888 |
- Submission date
- 10/08/2011
- Registration date
- 10/08/2011
- Last edited
- 04/04/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Mr Karl Harvey
Scientific
Scientific
Cancer Research UK Liverpool Cancer Trials Unit
200 London Road
Liverpool
L3 9TA
United Kingdom
Study information
| Study design | Both; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice |
| Study type | Treatment |
| Scientific title | Phase II trial of alemtuzumab, dexamethasone and lenalidomide followed by randomisation to lenalidomide maintenance versus no further treatment for high-risk CLL (NCRI CLL210) |
| Study acronym | CLL210 (CamDexRev) |
| Study objectives | All patients will receive induction therapy for 24 weeks with alemtuzumab, dexamethasone and lenalidomide (CamDexRev). Patients with stable or progressive disease (SD/PD) will receive no further trial treatment and will be managed at the discretion of local investigator. Patients who achieve a CR or PR may elect to have an allogeneic stem-cell transplant. Those responders who decide not to have a transplant will be randomised between continuing lenalidomide until disease progression or receiving no further trial treatment. Objectives: Primary:CR rate after 6 months of induction therapy Progression-free rate after 2 years of maintenance therapy, defined as the proportion of patients who are progression free and alive at 2 years Secondary Overall, complete and partial response rates following induction therapy Minimal residual disease (MRD) negativity rate following induction therapy Overall survival (time from start of study treatment to death) Progression-free survival (time from initiation of study treatment to progression or death) Time to treatment failure (time from initiation of study treatment to treatment failure defined as progression, death or initiation of alternative treatment due to failure to achieve CR or PR) Duration of response (time from first achievement of CR or PR to first time of progression or death) Toxicity Quality of life Descriptive summary of Progression-free and overall survival among transplant-eligible patients These will be estimated separately for the induction and the randomised phases of the study. |
| Ethics approval(s) | ref: 11/H1005/10 |
| Health condition(s) or problem(s) studied | Leukaemia |
| Intervention | Induction phase: Alemtuzumab, Subcutaneous, 30mg od on days 1, 3 and 5 of weeks 7-22 Induction phase: dexamethasone, Taken orally, 40mg od, day 1-4 of weeks 1, 3, 5, 7, 9, 11, 13 and 15. Induction phase: Lenalidomide, Taken orally, 5mg od, days 1-7 on weeks 3-4 and 10mg od, days 1-7 of weeks 5-24.; Induction phase: Lenograstim, Subcutaneous, 263µg od, days 1, 3 and 5 on weeks 5-8 plus whenever neutrophils <1.0x10^9/l; Maintenance: Lenalidomide, 10mg, od until disease progression; Follow Up Length: 30 month(s); Study Entry : Registration and One or More Randomisations |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Alemtuzumab, dexamethasone, lenalidomide |
| Primary outcome measure | 1. Complete response (CR) 2. Complete response with incomplete blood count recovery (CRi) rate after 6 months |
| Secondary outcome measures | 1. Progression-free rate after 2 years of maintenance therapy, defined as the proportion of patients 2. Toxicity 3. Cumulative dose of individual drugs administered 4. Overall, complete and partial response rates 5. Minimum Residual Disease (MRD) negativity rate 6. MRD-negative CR rate 7. Overall survival 8. Progression-free survival (progression or death) 9. Event-free survival (progression, death or further induction treatment) 10. Response duration 11. Quality of life |
| Overall study start date | 01/09/2011 |
| Completion date | 01/03/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 85; UK Sample Size: 85 |
| Total final enrolment | 64 |
| Key inclusion criteria | 1. CLL/SLL requiring treatment by IWCLL 2008 criteria 2. At least one of the following criteria should be met: 2.1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia 2.2. Massive (i.e. at least 6cm below the left costal margin) or progressive or symptomatic splenomegaly 2.3. Massive (i.e. at least 10cm in longest diameter) or progressive or symptomatic lymphadenopathy 2.4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months from a baseline value of at least 30x109/l and not due to causes other than CLL. 2.5. Constitutional symptoms defined as at least 10% unintentional weight loss within the previous 6 months, significant fatigue preventing usual activities, or fever of at least 38°C for at least 2 weeks or night sweats for at least one month in the absence of infection 3. High risk CLL/SLL defined by at least one of the following criteria: 3.1. TP53 deletion or mutation affecting at least 20% of CLL cells 3.2. Resistant (SD/PD) to fludarabine-containing combination therapy 3.3. Relapse within 12 months of responding to fludarabine-containing combination therapy 3.4. No prior treatment with alemtuzumab or lenalidomide 4. CLL not known to be resistant to glucocorticoids 5. No more than 3 previous treatment episodes for CLL 6. WHO performance status 0-2 7. Aged at least 18 years 8. Written informed consent 9. Male and female participants 10.Lower age limit 18 years, no age limit |
| Key exclusion criteria | 1. Neutrophil count less than 0.5x109/l or platelet count less than 25x109/l 2. Uncontrolled auto-immune haemolytic anaemia or thrombocytopenia 3. Active infection 4. Active gastritis or peptic ulcer disease 5. Uncontrolled diabetes mellitus or hypertension 6. History of recurrent thromboembolism 7. Seropositivity for HIV, HCV or HBV (surface antigen or core antibody) 8. Renal impairment (creatinine clearance less than 30ml/min) 9. Hepatic impairment (serum bilirubin more than twice the upper limit of normal unless due to Gilbert's syndrome or CLL) 10. Concurrent treatment with glucocorticoids equivalent to more than prednisolone 20mg 11. Presence or history of CNS disease (either CNS lymphoma or leukaemic meningitis) 12. History of Richter transformation 13. Allergy to rat proteins 14. Concomitant malignancies except adequately treated localised non-melanoma skin cancer and cancers that have been in remission for at least 5 years 15. Major surgery within 28 days prior to registration 16. Any serious underlying medical or psychological conditions, which could impair the ability of the patient to participate in the trial or compromise ability to give informed consent 17. Treatment within a clinical trial within 30 days prior to trial entry 18. Adult patient under tutelage (not competent to sign informed consent) 19. Pregnant or lactating women 20. All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom 21. Women taking the oral contraceptive pill within 4 weeks of study registration owing to an increased risk of thromboembolism |
| Date of first enrolment | 01/09/2011 |
| Date of final enrolment | 01/03/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cancer Research UK Liverpool Cancer Trials Unit
Liverpool
L3 9TA
United Kingdom
L3 9TA
United Kingdom
Sponsor information
University of Liverpool (UK)
University/education
University/education
Cancer Research UK
Liverpool Cancer Trials Unit
200 London Road
Liverpool
L3 9TA
England
United Kingdom
| Website | http://www.liv.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Industry
Celgene International
No information available
Chugai Pharma (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | results | 11/04/2017 | No | No | |
| Results article | results | 01/12/2020 | 17/02/2020 | Yes | No |
| Plain English results | 04/04/2022 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
04/04/2022: Plain English results added.
17/02/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
06/03/2018: Publication reference added.
29/02/2016: No publications found, verifying study status with principal investigator.
